In this planning grant to establish a Program of Excellence in Biomedical Computing, the University of Pennsylvania and the Children's Hospital of Philadelphia propose to develop a new organization that will serve as a central conduit of biomedical computing research tying together the activities of three schools and six research institutes. The organization will consist of a scientific steering committee with internal and external members to oversee research activities, an oversight committee to provide institutional support, an executive committee to govern day-to-day activities, and an office of education to coordinate the training activities. The organizational structure will be generated under the umbrella of the Penn Genomics Institute and the Penn Center for Bioinformatics to leverage existing resources. Interdisciplinary research interactions will be promoted by funding 12 new seed grants (made possible by matching funds) focusing on comparative approaches to biomedical knowledge discovery. In the first year, four projects will be funded: (1) pattern discovery in comparative genomics; (2) computational phylogeny reconstruction; (3) comparative text mining for cancer research; and (4) comparative informatics approach to sickle-cell disease. In subsequent years, new projects will be added to the first four through an internal solicitation for proposals. The Scientific Steering Committee will review these proposals and four new projects will be funded in Years 2 and 3. Each year, existing projects will be reviewed and at the end of the planning grant, all projects will be reviewed for consolidation into a small number of high impact projects. New interactions between existing computational faculty and biomedical faculty will be encouraged by holding opportunity presentation retreats to introduce researchers from complementary fields to biological problems and computational methods. Faculty basic education seminars will be held monthly where basic concepts like "transcription" will be discussed in a highly interactive format. The existing core facility for bioinformatics will be augmented with additional high-performance computing hardware, support for teaching basic computational biology tools, and a facility to coordinate dissemination of software tools developed from this grant. An existing PhD level training program in biomedical computing will be supplemented to provide research experience for undergraduates and masters students.